Interleukin 17 treatment prolongs CXCL 1 mRNA half-life via TRAF 5 and the splicing regulatory factor SF 2 / ASF

Interleukin 17 (IL-17) promotes expression of chemokines and cytokines via induction of gene transcription and post-transcriptional stabilization of mRNA. We show that IL-17 enhanced the stability of CXCL1 and other mRNAs through a pathway that involves Act1, TRAF2 or TRAF5 and the splicing factor SF2/ASF. TRAF2/TRAF5 were necessary for IL-17 to signal CXCL1 mRNA stabilization. Furthermore, IL-17 promoted formation of complexes between TRAF5/ TRAF2, Act1 and SF2/ASF. Overexpression of SF2/ASF shortened while depletion of SF2/ASF prolonged CXCL1 mRNA half-life. SF2/ASF bound chemokine mRNA in unstimulated cells while the SF2/ASF-mRNA interaction was markedly diminished following stimulation with IL-17. These findings define an IL-17-induced signaling pathway that links to the stabilization of selected mRNAs through Act1, TRAF2/5 and the RNA binding protein SF2/ASF.